Preterm birth, the leading cause of neonatal mortality in the United States, is also associated with a number of chronic health conditions and developmental disabilities that cause lifelong consequences. In Puerto Rico, the preterm birth rate is 17.7% of live births. At 50% above the U.S. average, it is the highest rate of any United States jurisdiction, below only Malawi (18.1%) globally. The researchers investigations suggest that the higher preterm birth rates in Puerto Rico cannot be explained by changes in obstetric practices, and that there is compelling preliminary evidence that exposure to hazardous chemicals contributes to preterm birth. Puerto Rico has 16 active Superfund sites and 200+ hazardous waste sites. Risk of exposure to contamination is high as many of these sites are unlined landfills that overlie Karst aquifers which present highly susceptible pathways for exposure to contamination. PROTECT (Puerto Rico Testsite for Exploring Contamination Threats) brings together multidisciplinary researchers study the transport, exposure, health impact and remediation of contaminants, with particular attention to chlorinated solvents and phthalates commonly found at Superfund sites, as both suspect and model agents in the high to preterm birth rates in Puerto Rico. To do so, PROTECT uses an innovative, holistic, source-to-outcome structure, integrating epidemiological, toxicological, and analytical, fate-transport, and remediation studies along with a unified sampling infrastructure, a centralized, indexed data repository and a data management system. Administrative, research translation, training and community engagement cores engage and inform stakeholders, provide knowledge-transfer activities to the greater SRP and environmental health community, and provide extensive cross-disciplinary training. PROTECT is responsive to NIEHS, EPA and CDC strategic goals, and addresses priority areas identified by the Institute of Medicine Committee on preterm birth. Since the Center's inception in 2010, PROTECT researchers have obtained significant and novel results indicating 1) extensive groundwater contamination in the northern Karst region of Puerto Rico; 2) potential mechanisms by which chemicals can stimulate preterm birth; and, 3) suspect chemicals that are elevated in the women in this study. The investigators have also developed a new environmentally-friendly technique for efficient decontamination of groundwater and an improved large-volume urinalysis technique. Research results have been documented in over 50 journal papers and 2 full patent applications. In addition, over 480 pregnant study subjects have been enrolled (200 of whom have completed their pregnancies), and over 70 trainees have participated in the Center. PROTECT will build on these successes with continued research and training to provide the much needed understanding of the role of hazardous chemicals and other environmental factors in preterm birth, and to develop new methods for contaminant remediation in Puerto Rico and beyond. This work will advance environmental health science in general, and potentially lead to a reduction in preterm birth rates.